Anesthetic technique and the cytokine and matrix metalloproteinase response to primary breast cancer surgery.

BACKGROUND: Breast cancer is the most common malignancy in women. Surgery remains the most effective treatment. Several perioperative factors, including the surgical stress response, many anesthetics and opioids, adversely affect immune function. Regional anesthesia-analgesia attenuates perioperative immunosuppression. We tested the hypothesis that patients who receive combined propofol/paravertebral anesthesia-analgesia (propofol/paravertebral) exhibited reduced levels of protumorigenic cytokines and matrix metalloproteinases (MMPs) and elevated levels of antitumorigenic cytokines compared with patients receiving sevoflurane anesthesia with opioid analgesia (sevoflurane/opioid). METHODS: Primary breast cancer surgery patients were randomized to propofol/paravertebral (n = 15) or sevoflurane/opioid (n = 17) and preoperative and postoperative serum concentrations of 11 cytokines (interleukin 1ß [IL-1ß], IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon γ, and tumor necrosis factor α) and 3 MMPs (MMP-1, MMP-3, and MMP-9) were measured. RESULTS: Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathologic diagnosis. Pain scores were lower at 1 and 2 hrs with paravertebral analgesia compared with morphine but similar at 24 hrs. Patients in the propofol/paravertebral group showed a greater percentage decrease in postoperative compared with preoperative IL-1ß (median [quartiles], -26% [-15% to -52%] versus -4% [-14% to 2%], P = 0.003), a significant attenuation in elevated MMP-3 (2% [-39% to 12%] versus 29% [23%-59%], P = 0.011) and MMP-9 (26% [13%-54%] versus 74% [50%-108%], P = 0.02), and a significant increase in IL-10 (10% [5%-33%] versus -15% [20% to -2%], P = 0.001) compared with sevoflurane/opioid group. No significantly different changes in IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, interferon γ, tumor necrosis factor α, or MMP-1 were observed between the 2 groups. CONCLUSIONS: Propofol/paravertebral anesthesia-analgesia for breast cancer surgery alters a minority of cytokines influential in regulating perioperative cancer immunity. Further evaluation is required to determine the significance of these observations.

Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis.

BACKGROUND: Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia. METHODS: In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia-epidural analgesia or general anesthesia-opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen. RESULTS: After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17-78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22-0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia. CONCLUSIONS: Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.

The feasibility of patient-controlled paravertebral analgesia for major breast cancer surgery: a prospective, randomized, double-blind comparison of two regimens.

BACKGROUND: Paravertebral analgesia is useful for breast surgery. Patient controlled analgesia by IV or epidural routes is well established for delivering postoperative analgesia. Our objective was to apply patient control to paravertebral analgesia and evaluate the efficacy and tolerability of two distinct dosing regimens. METHODS: Patients undergoing major breast cancer surgery were recruited for this prospective, double-blind, randomized trial of two patient-controlled paravertebral analgesia regimens: 19 patients received levobupivacaine 0.2% at 8 mL/h with 3-mL bolus and 15-min lockout (15-min lockout group); 18 received levobupivacaine 0.2% at 4 mL/h with 8-mL bolus and 30-min lockout (30-min lockout group). Our primary outcome was dynamic pain scores (visual analog scale) at 4-hourly intervals for 36 h. Secondary outcomes were resting pain scores, rescue analgesia requirements, volume of levobupivacaine administered, demands for levobupivacaine, levobupivacaine boluses received, and patient satisfaction. RESULTS: Resting and dynamic pain scores were comparable in the groups. Two 15-min lockout patients and five 30-min lockout patients required rescue analgesia (P = 0.23). Patients received 400 +/- 95 mL and 330 +/- 130 mL levobupivacaine in 15-min and 30-min lockout groups, respectively (P = 0.012). The 15-min lockout group requested a bolus 75 +/- 16 times; the 30-min lockout group requested it 69 +/- 14 times (P = 0.40). However, the 15-min lockout group received 39 +/- 22 boluses and the 30-min lockout group only 24 +/- 16 (P = 0.02). Systolic pressure, heart rate, respiratory rate, sedation scores, nausea, antiemetic requirement, and satisfaction scores were similar in each group. CONCLUSIONS: Patient-controlled paravertebral analgesia for breast cancer surgery, with either regimen, provided satisfactory analgesia and was well tolerated.

Pharmacokinetics of levobupivacaine, fentanyl, and clonidine after administration in thoracic paravertebral analgesia.

BACKGROUND AND OBJECTIVES: There is little knowledge of the pharmacokinetics of local anesthetics and adjunctive analgesics after paravertebral blockade. We evaluated the pharmacokinetics of low-dose levobupivacaine, fentanyl, and clonidine after paravertebral analgesia for breast surgery. METHODS: Thirty-eight patients receiving paravertebral analgesia for breast surgery received a 19-mL paravertebral bolus of levobupivacaine 0.25% combined with a 1-mL volume of saline (group L, 13 patients), fentanyl 50 microg (group LF, 13 patients), or clonidine 150 microg (group LC, 12 patients) followed 1 hour later by infusion of levobupivacaine 0.1% (L), levobupivacaine 0.05% with fentany l 4 microg/mL (LF), or levobupivacaine 0.05% with clonidine 3 microg/mL (LC), respectively. Plasma concentrations of study drugs were determined at intervals up to 24 hours after bolus injection. RESULTS: There was rapid absorption of levobupivacaine after bolus with mean (standard deviation) maximum plasma concentration (Cpmax) of 0.51(0.24) microg/mL in a median time to maximum concentration tCpmax of 15 minutes. Mean Cpmax fentanyl and clonidine after bolus were 0.62 (0.37) and 0.79 (0.23) ng/mL, in a median tCpmax of 15 and 22.5 minutes, respectively. Mean Cpmax levobupivacaine after infusion was 0.47 (0.41) microg/mL in a median tCpmax of 24 hours. There was progressive accumulation of fentanyl and clonidine at 24 hours with a mean Cpmax of 0.72 (0.33) and 1.74 (0.70) ng/mL, respectively. CONCLUSIONS: After paravertebral bolus and infusion administration, Cpmax levobupivacaine was within the safe range. Cpmax fentanyl and clonidine were less than the effective levels after IV administration, suggesting that their analgesic effect may be partly attributed to a peripheral mechanism of action.

Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?

BACKGROUND: Regional anesthesia is known to prevent or attenuate the surgical stress response; therefore, inhibiting surgical stress by paravertebral anesthesia might attenuate perioperative factors that enhance tumor growth and spread. The authors hypothesized that breast cancer patients undergoing surgery with paravertebral anesthesia and analgesia combined with general anesthesia have a lower incidence of cancer recurrence or metastases than patients undergoing surgery with general anesthesia and patient-controlled morphine analgesia. METHODS: In this retrospective study, the authors examined the medical records of 129 consecutive patients undergoing mastectomy and axillary clearance for breast cancer between September 2001 and December 2002. RESULTS: Fifty patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia, and 79 patients had general anesthesia combined with postoperative morphine analgesia. The follow-up time was 32 +/- 5 months (mean +/- SD). There were no significant differences in patients or surgical details, tumor presentation, or prognostic factors. Recurrence- and metastasis-free survival was 94% (95% confidence interval, 87-100%) and 82% (74-91%) at 24 months and 94% (87-100%) and 77% (68-87%) at 36 months in the paravertebral and general anesthesia patients, respectively (P = 0.012). CONCLUSIONS: This retrospective analysis suggests that paravertebral anesthesia and analgesia for breast cancer surgery reduces the risk of recurrence or metastasis during the initial years of follow-up. Prospective trials evaluating the effects of regional analgesia and morphine sparing on cancer recurrence seem warranted.

Increased incidence of postoperative cognitive dysfunction 24 hr after minor surgery in the elderly.

PURPOSE: Postoperative cognitive dysfunction (POCD) is evident in 26% of elderly patients seven days after major non-cardiac surgery. Despite the growing popularity of day surgery, the influence of anesthetic techniques on next day POCD has not been investigated. Therefore, we evaluated the incidence of POCD and changes in serum markers of neuronal damage (S-100ss protein and Neuron-Specific Enolase), 24 hr after single-agent propofol or sevoflurane anesthesia in elderly patients undergoing minor surgery. METHODS: Patients (n = 30, mean age 73, range 65-86 yr) coming for cystoscopy or hysteroscopy, were randomized, in an observer-blind design, to receive either single-agent propofol or sevoflurane anesthesia. Changes in neuropsychological tests (the Stroop test and the modified Word-Recall Test), 24 hr postoperatively were compared with age-matched control subjects (n = 15) using Z-score analysis. Changes in S-100beta protein and Neuron-Specific Enolase levels were also documented. RESULTS: POCD was present in 7/15 [47% (95% confidence interval (CI) 21 to 72%)] patients who received propofol and 7/15 [47% (95% CI 21 to 72%)] patients who received sevoflurane, compared with 1/15 [7% (95% CI 6 to 19%)] control patients, P = 0.03. S-100beta protein and Neuron-Specific Enolase levels were not significantly different in anesthetized patients postoperatively compared with preoperative values. CONCLUSION: The incidence of POCD in elderly patients on the first day after minor surgery is higher than previously reported for seven days after major surgery, and is increased after both propofol and sevoflurane anesthesia, compared with age-matched controls. S-100beta protein and Neuron-Specific Enolase levels were unaffected by anesthetic technique.

Continuous gastric decompression for postoperative nausea and vomiting after coronary revascularization surgery.

Postoperative nausea and vomiting is common after cardiac surgery and may contribute to significant morbidity. Gastric decompression during anesthesia has been used for postoperative nausea and vomiting prophylaxis in shorter duration noncardiac surgery with conflicting results. We tested the hypothesis that gastric decompression during elective coronary revascularization surgery with cardiopulmonary bypass and continued afterwards until tracheal extubation would reduce the incidence of vomiting or retching and nausea. In a prospective, randomized, cohort study, 104 patients with at least 2 Apfel's risk factors for postoperative nausea and vomiting were allocated to receive a gastric tube on free gravity drainage after induction of anesthesia (n = 52) or to a control group (n = 52). The gastric tube was removed simultaneously with tracheal extubation postoperatively. The primary outcome measure was the incidence of vomiting or retching. Secondary outcomes included the incidence and severity of nausea measured on a visual analog scale. The incidence of vomiting or retching was 13.4% in patients with gastric decompression, compared with 11.5% in the control group (P = 0.7). Similarly, there was no statistically significant difference between the two groups in the incidence of nausea (32.7% versus 25.0%, P = 0.6), median severity of nausea on a visual analog scale at 12 h (25; range, 0-55 mm versus 30; range, 0-60 mm, P = 0.4), or antiemetics administration (38.5% versus 28.8%, P = 0.3). Continuous gastric decompression during coronary revascularization surgery and afterwards until tracheal extubation did not reduce the incidence of vomiting or retching or the incidence and severity of nausea in these patients.